Graft-versus-host disease: pathophysiological and clinical aspects.

Graft-versus-host disease (GVHD) is a syndrome observed after allogeneic marrow transplantation and presumably mediated by donor T lymphocytes reactive against the tissues of the recipient. Clinically relevant acute GVHD develops in 35-50% of patients given HLA-identical marrow grafts within the first 100 days of transplantation. The main target organs are skin, liver, and intestinal tract. Approximately one half of the patients with moderately severe to severe disease die, usually from associated infections. Prevention of acute GVHD by placing the patient in protective isolation, immunosuppressive treatment after grafting, or removal of donor lymphocytes from the marrow inoculum has, as yet, not been uniformly successful. Treatment of established GVHD involves the use of immunosuppressants such as glucocorticosteroids, antithymocyte globulin, cyclosporine, and monoclonal antibodies. Chronic GVHD usually develops 100-500 days after transplantation and affects about 45% of all long-term survivors. The main target organs are the same as those of acute GVHD and, in addition, lacrimal and salivary glands, and mucous and serous membranes; the clinical picture resembles that of a number of collagen-vascular diseases. The incidence of chronic GVHD is higher in patients with previous acute GVHD and it increases with patient age. Treatment involves immunosuppressive and cytotoxic drugs. Patients are highly susceptible to bacterial and fungal infections that are lethal in a small proportion of patients.